The flavonoid, fisetin, inhibits UV radiation-induced oxidative stress and the activation of NF-kappaB and MAPK signaling in human lens epithelial cells.
OBJECTIVE
Ultraviolet (UV) radiation-induced oxidative stress plays a significant role in the progression of cataracts. This study investigated the photoprotective effect of fisetin on UV radiation-induced oxidative stress in human lens epithelial cells and the possible molecular mechanism involved.


METHODS
SRA01/04 cells exposed to different doses of ultraviolet B (UVB) were cultured with various concentrations of fisetin and subsequently monitored for cell viability by the 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of fisetin on the generation of reactive oxygen species (ROS) of SRA01/04 cells was determined by flow cytometry. Translocation of nuclear factor kappa-B (NF-kappaB) was examined by immunocytochemistry. Expression of NF-kappaB/P65, inhibiter kappa B (IkappaB), and mitogen activated protein kinase (MAPK) proteins were measured by western blot.


RESULTS
Treatment of SRA01/04 cells with fisetin inhibited UVB-induced cell death and the generation of ROS. Fisetin inhibited UVB-induced activation and translocation of NF-kappaB/p65, which was mediated through an inhibition of the degradation and activation of IkappaB. Fisetin also inhibited UVB-induced phosphorylation of the p38 and c-Jun N-terminal kinase (JNK) proteins of the MAPK family at various time points studied.


CONCLUSIONS
The flavonoid, fisetin, could be useful in attenuation of UV radiation-induced oxidative stress and the activation of NF-kappaB and MAPK signaling in human lens epithelial cells, which suggests that fisetin has a potential protective effect against cataractogenesis.
Yao
Ke
K
Eye Center, Affiliated Second Hospital, College of Medicine, Zhejiang University, Hangzhou, China. xlren@zju.edu.cn
Zhang
Li
L
Zhang
Yidong
Y
Ye
PanPan
P
Zhu
Ning
N
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000528:radiation effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays
D005419:Flavonoids; D044948:Flavonols; D020672:I-kappa B Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D020928:Mitogen-Activated Protein Kinases; C017875:fisetin